Drug dependence can be associated with serious health problems. Researchers are interested in understanding why these addictions develop. Scientists knew that the reinforcing properties of addictive drugs were dependent on the activity of the mesolimbic dopamine neurons, but the underlying genetic factors were poorly understood. They hypothesized that the ras-specific guanine-nucleotide releasing factor 2 (RASGF2) could be related to the reinforcement of addictive drugs because it interacts with the ERK pathway (a signal transduction cascade) that seems to mediate drug-induced reinforcement processes in the mesolimbic system. They wanted to test this hypothesis by looking at the role of Ras-GRF2 in alcohol-related behavior and mesolimbic dopamine (DA) neuron function.

Methods

Mouse Models
The researchers used mouse models to look at the functions of Ras-GF2. In the first study they compared the Ras-GF2 mRNA whole-brain expression levels between two groups of mice: high alcohol-preferring (HAP1) and low alcohol-preferring (LAP1) mice.

They then compared ethanol consumption in Rasgr2-/- (without the gene) to wild type (WT) mice. Researchers analyzed which drinking bottle the mice preferred when they were freely able to choose between water or ethanol solution.

Next, the researchers wanted to understand the effects of Ras-GF2 on dopamine release. To do this they carried out microdialysis to measure the extracellular DA levels in Rasgrf2-/- and WT mice.

Humans

Since researchers expected that impaired firing of DA neurons could result in dysregulation of reward systems they wanted to see if variations in the human RASGRF2 gene affected these reward mechanisms. They used boys in this study because the original link between alcohol drinking and the RASGRF2 gene was only observed in males. In this study, they looked at the activation of certain parts of the brain. They used the monetary incentive delay task as a functional neuroimaging reward model, to simulate the reward response associated with alcohol.

Results

Mouse Models

Researchers found a significantly higher increase in Rasgrf2 mRNA expression in HAP mice compared to LAP mice (Table 1.) This suggests that Ras-GRF2 is associated with alcohol preference levels.

They also found that Rasgrf2-/- mice showed a significant reduction in ethanol intake compared to the controls, with a threefold reduction at the highest ethanol concentration (Fig. 1A). These mice also showed reduced ethanol preference, which was determined by measuring the percentage of ethanol intake compared to water intake (Fig. 1B).

Researchers also found that ethanol-induced dopamine release and DA neuron excitability is impaired in Rasgrf2-/- mice.

Humans

In the neuroimaging study they found that the RASGRF2 haplotype is associated the response in brain reward areas and drinking behavior (Fig. 4).

Discussion

From these results the researchers showed that Ras-GRF2 influences alcohol-induced reinforcement by controlling mesolimbic DA release. Their findings suggest also that other genetic factors controlling DA neuron excitability may also be related to the abuse of drugs. These results could be useful in finding treatments for addictions, by targeting this signal transduction pathway and altering the Ras-GRF2 gene.

POPULAR PRESS ARTICLE

One of the many challenges associated with translating scientific articles into popular press reports is making the information accessible to a wide-range of people. In order to do this, reporters change the language and writing style used so that the audience can understand the research being presented (Kua et al., 2005). Unfortunately, through this process reporters often modify what was said in the scientific journal. Additionally, popular press articles want to engage and entertain their readers even if this means some of the facts are not clear. The popular press article published by Fox News in response to the PNAS scientific publication illustrates some of the ways in which information can be mistranslated when moving from one context to another.

The news article begins by introducing the study and providing the reader with some basic information about the effects of alcohol. The article then goes on to briefly describe the various methods and results of the research. The article ends with statistical information about alcohol intake. While the article may seem well structured, not all the content is relevant and some information is left out.

In the Fox News article, there are numerous instances where the author does not provide the reader with enough information in terms of the methods of the study. For example, when discussing the tests done on mice the reporter states that, “They found the lack of RASGRF-2 was linked to a significant reduction in alcohol-seeking activity.” This idea of “alcohol-seeking activity” is ambiguous and never clearly defined. In this context, the results stated have no support because the methods by which they were obtained are not explained (Kua et al., 2005). Also when the article discusses the study of neuroimaging in 14-year-old boys, the report does not give reasons for why the scientists decided to conduct this test. In this case, the reader does not have enough detail to understand this portion of the study. For example, it was never explained why the researchers only used males in this test, which seems like important information. By giving vague explanations of the tests that were carried out the findings of these studies cannot be fully appreciated. Reporters need to provide the readers with enough information so that they know exactly what was accomplished in the study.

Another aspect that is not included in the popular press article is “what parts of the puzzle remain unsolved” (Kua et al., 2005). The popular press article not only provides little evidence in support of the findings, it also fails to address avenues for future research. The reporter makes it seem as though everything about the RASGRF2 gene is now known, when in reality a lot is left to be determined. In the PNAS journal article, the researchers even state that there are other genetic factors that affect dopamine neuron excitability, which also cause an increased response to alcohol. The Fox News article never mentions these factors. It is important the readers know the implications of this study and where research with this gene is headed.

Another problem that arises in popular press articles is the need to entertain audiences. In order to keep the audience interested, the Fox News reporter provides the reader with information and statistics related to binge drinking that were never mentioned in the scientific study. The presentation of outside information in some ways takes away from what was actually being said in the scientific paper. Examples of these stats include, “Worldwide, some 2.5 million people die each year from the harmful use of alcohol, accounting for about 3.8 percent of all deaths, according to the World Health Organisation.” It is important to realize that the researchers of this study do not believe that genetic variations in the Ras-GRF2 gene are responsible for these deaths. The popular press needs to ensure that the information they present is directly related to the study being analyzed and does not set up the reader to draw false conclusions (Kua et al., 2005).

While there are many faults in this popular press article, there are also things that were well done. For example, while the statistical information seems randomly inserted into the report, it does have some value. This information about excessive alcohol intake illustrates why the study of the “binge-drinking gene” is important and how this study is relevant to the reader. It gives the reader incentive to keep reading. The reporter also includes quotes from Gunter Schumann, one of the researchers involved in the original study. These quotes give the article more credibility because the researcher himself is talking about the Ras-GRF2 gene in a way that the general public can understand. One would hope that his translation is true to the research findings.

Conclusion

Kua et al. assert that the only way translation of scientific material can work is if the findings are understood in terms of the research methods that were employed and the goals that the scientists were trying to achieve. While this is difficult to accomplish, it can be done as long as the reporters provide their readers with enough context and information. Kua et al. believe that the reporter’s role in the translation process is threefold: they must act as an “intermediary”, a “watchdog”, and provide the reader with “tools” with which they can use the information presented. As an intermediary, the popular press reporter does a fairly good job of translating what was said in the scientific paper, without including any personal opinions or embellishments to alter the readers perceptions of the information. At the same time, a lot of information is lost in this translation process or simply not included which is one of the biggest weaknesses of the popular press article. The "watchdog" element is the inclusion of "the discussion of social and ethical implications of the work, the interest in the wider picture" in order to stimulate not only interest but also encourage thinking about these issues as they relate to public concern (Kua et al., 2005). The Fox News article, does not include much about the implications of the study's findings, which makes it difficult to understand the importance of the study. As a "watchdog" the reporter should have given the reader more information about future research and how this information could effect the general public. Finally, as a "tool-giver" the reporter does provide easy to understand definitions and descriptions for the reader, but fails to give a solid discussion of the context of the study, which is essential according to Kua et al.

Glossary

ERK pathway-is a chain of proteins in the cell that communicates a signal from a receptor on the surface of the cell to the DNA in the nucleus of the cell (Orton, 2005)

Microdialysis-is a minimally-invasive sampling technique that is used for continuous measurement of free, unbound analyte concentrations in the extracellular fluid of virtually any tissue (Wikipedia)